From Nature magazine
More than 40% of tuberculosis infections that are resistant to front-line treatments are also resistant to some common backup drugs, according to research published this week in The Lancet1.
Efforts to control tuberculosis are being hampered by the emergence of multidrug-resistant (MDR) strains of the disease, which resist treatment with two front-line antibiotics, rifampicin and isoniazid. In some parts of the world, as many as 50% of tuberculosis cases are resistant to these drugs2. Alternative treatment options are toxic and expensive, relying on second-line drugs that are not as effective and must be given in lengthy courses. Unfortunately, the majority of MDR tuberculosis cases occur in developing countries that can’t afford the several billion dollars that the global Stop TB Partnership estimates3 will be required to combat the disease.
More recently, strains of tuberculosis have emerged that are resistant not only to front-line antibiotics, but also to one or more drugs within each of the two most important classes of second-line drugs — broad-spectrum antibiotics called fluoroquinolones, and injectable agents (amikacin, capreomycin and kanamycin). This extensively drug-resistant (XDR) tuberculosis heralds a disturbing trend towards infections that are virtually untreatable.
“It is critical that we take steps now in diagnosing, treating and preventing MDR tuberculosis so that it doesn’t turn into XDR tuberculosis,” says Peter Cegielski, medical officer for the division of tuberculosis elimination at the US Centers for Disease Control and Prevention in Atlanta, Georgia, and a co-author of the Lancet study1.
Under the radar
Cegielski and his colleagues investigated the prevalence of resistance to second-line drugs among 1,278 people diagnosed with MDR tuberculosis in eight countries — most of which are on the list of nations with a high MDR-tuberculosis burden. They found that 43.7% of the study participants were infected with a tuberculosis strain that was resistant to at least one second-line drug, and 6.7% of the infections proved to be XDR tuberculosis.
The team also identified factors associated with a risk of developing resistance to second-line drugs, and found that the most significant was previous treatment with the same drugs. “By identifying the risk factors, we can help shape practice to ensure that patients are diagnosed and treated properly,” says Cegielski.
Until now, there has been no clear understanding of acquired resistance to second-line drugs, because countries where MDR tuberculosis is rife have limited laboratory resources and lack consistent testing. Paul van Helden, a tuberculosis researcher at the University of Stellenbosch in South Africa, says that the Lancet study provides a baseline against which to measure future progress.
Sven Hoffner, a clinical mycobacteriologist at the Swedish Institute for Communicable Disease Control in Solna, says that drug-resistant tuberculosis is "a manmade problem", often because drugs are not available or of poor quality. The key to controlling it, he says, is to detect and treat cases quickly. However, diagnosis can take up to three months, during which the disease can still be transmitted.